Hemocompatibility and anti-fouling behavior of multilayer biopolymers immobilized on gold-thiolized drug-eluting cardiovascular stents

Colloids Surf B Biointerfaces. 2019 Jan 1:173:470-477. doi: 10.1016/j.colsurfb.2018.10.014. Epub 2018 Oct 9.

Abstract

To solve the thrombosis and restenosis problem in cardiovascular stent implantation for cardiovascular artery disease, chondroitin 6-sulfate (ChS) with heparin (HEP) have been used as drug carrier layers and alternatively covalently bonded on gold (Au)-dimercaptosuccinic acid (DMSA)-thiolized cardiovascular metallic (SUS316 L stainless steel, SS) stents. Sirolimus, a model drug, was encapsulated in the ChS-HEP alternative layers. The behavior of the drug in releasing and suppressing the growth of smooth-muscle cells (SMCs) was evaluated with 5-layer CHS-HEP coating on the SS stents. Moreover, hemocompatibility of blood clotting time and platelet adhesion was performed. The results showed that the 5-layer ChS-HEP-modified SS stents displayed the greatest hemocompatibility, showing prolonged blood clotting time of the activated partial thrombin time (> 500 s) and less platelet adhesion to reduce thrombosis. Furthermore, sirolimus can be released continuously for more than 40 days with the 5-layer ChS-HEP coating and is beneficial for inhibiting the growth of SMCs; however, it does not affect the proliferation of endothelial cells, which can avoid restenosis formation. Therefore, the multilayers of ChS-HEP grafted onto the Au-DMSA-cardiovascular SS stents provide high potential for use as drug eluting stents.

Keywords: Cardiovascular metallic stents; Chondroitin 6-sulfate; Hemocompatibility; Heparin; Restenosis; Thrombosis.

MeSH terms

  • Blood Coagulation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chondroitin Sulfates / chemistry*
  • Coated Materials, Biocompatible / chemistry*
  • Coated Materials, Biocompatible / pharmacology
  • Drug Compounding / methods
  • Drug-Eluting Stents*
  • Gold / chemistry*
  • Heparin / chemistry*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Partial Thromboplastin Time
  • Platelet Adhesiveness / drug effects
  • Platelet-Rich Plasma
  • Sirolimus / chemistry
  • Sirolimus / pharmacology*
  • Stainless Steel / chemistry
  • Stainless Steel / pharmacology
  • Succimer / chemistry

Substances

  • Coated Materials, Biocompatible
  • Stainless Steel
  • Gold
  • Heparin
  • Chondroitin Sulfates
  • Succimer
  • Sirolimus